title: Identification of copy number variants associated with BPES-like phenotypes.
abstract: Blepharophimosis-Ptosis-Epicanthus inversus syndrome (BPES) is a well-characterized rare syndrome that includes an eyelid malformation associated with (type I) or without premature ovarian failure (type II). Patients with typical BPES have four major characteristics: blepharophimosis, ptosis, epicanthus inversus and telecanthus. Mutations in the FOXL2 gene, encoding a forkhead transcription factor, are responsible for the majority of both types of BPES. However, many patients with BPES-like features, i.e., having at least two major characteristics of BPES, have an unidentified cause. Here, we report on a group of 27 patients with BPES-like features, but without an identified genetic defect in the FOXL2 gene or flanking region. These patients were analyzed with whole-genome high-density arrays in order to identify copy number variants (CNVs) that might explain the BPES-like phenotype. In nine out of 27 patients (33%) CNVs not previously described as polymorphisms were detected. Four of these patients displayed psychomotor retardation as an additional clinical characteristic. In conclusion, we demonstrate that BPES-like phenotypes are frequently caused by CNVs, and we emphasize the importance of whole-genome copy number screening to identify the underlying genetic causes of these phenotypes.
authors.affiliation: Center for Human and Clinical Genetics, Leiden University Medical Center, Postzone S-6-P, Einthovenweg 20, 2333 CZ, Leiden, The Netherlands. a.c.j.gijsbers@lumc.nl
authors.forename: Antoinet C J
authors.initials: AC
authors.lastname: Gijsbers
authors.forename: Barbara
authors.initials: B
authors.lastname: D'haene
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Hilhorst-Hofstee
authors.forename: Marcel
authors.initials: M
authors.lastname: Mannens
authors.forename: Beate
authors.initials: B
authors.lastname: Albrecht
authors.forename: Joerg
authors.initials: J
authors.lastname: Seidel
authors.forename: David R
authors.initials: DR
authors.lastname: Witt
authors.forename: Melissa K
authors.initials: MK
authors.lastname: Maisenbacher
authors.forename: Bart
authors.initials: B
authors.lastname: Loeys
authors.forename: Ton
authors.initials: T
authors.lastname: van Essen
authors.forename: Egbert
authors.initials: E
authors.lastname: Bakker
authors.forename: Raoul
authors.initials: R
authors.lastname: Hennekam
authors.forename: Martijn H
authors.initials: MH
authors.lastname: Breuning
authors.forename: Elfride
authors.initials: E
authors.lastname: De Baere
authors.forename: Claudia A L
authors.initials: CA
authors.lastname: Ruivenkamp
mesh_terms: D016569:Blepharophimosis / Q000235:genetics*; D001763:Blepharoptosis / Q000235:genetics*; D002869:Chromosome Aberrations; D005143:Eyelids / Q000002:abnormalities; D005260:Female; D018628:Gene Dosage; D014644:Genetic Variation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D013577:Syndrome